The present invention relates to the treatment and prevention of bone diseases in humans, including osteoporosis in postmenopausal women, Paget""s Disease and hypercalcemia, by administration of a bisphosphonate in an inhalation form. The invention also relates to pharmaceutical inhalation compositions suitable for the treatment and prevention of bone diseases.
Bisphosphonates are known in the art as bone resorption inhibitors. Examples of bisphosphonates include, alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid; tiludronate, 4-chlorophenylthiomethylene bisphosphonatic acid; pamidronate, (3-amino-hydroxypropylidnen) bisphosphonic acid; etidronate, (1-hydroxyethylidene)bisphosphonic acid; residronate, 1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid; zoledronate, 2-(imidazol-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid; and the pharmaceutically acceptable salts of the above compounds.
Bisphosphonates, and their pharmaceutically acceptable salts, are useful in the treatment and prevention of bone diseases such as osteoporosis. Specifically, bisphosphonates are useful for the treatment of urolithiasis and are capable of inhibiting bone reabsorption. Bisphosphonates are also useful in lessening the risk of non-vertebral fractures in osteoporotic women and as a therapeutic agent for hypercalcemia and Paget""s disease.
Current treatments for the above conditions comprise administration of a pharmaceutically effective amount of a bisphosphonic acid in oral dosage forms such as tablets. Bisphosphonates may also be administered by intravenous methods. The benefits of bisphosphonates are observed by its effect on bone mass and density. However oral and intravenous dosage forms have very low bioavailability. In some instances, the bioavailability is less than 1%. Accordingly, it would be desirable to find a route of administration of bisphosphonates that substantially increases its bioavailability.
In addition, oral dosage forms of the free acid form of certain bisphosphonates, e.g. 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid, may result in gastric irritability, and therefore it would also be desirable to administer these bisphosphonates by a route that avoids such gastrointestinal problems.